Abstract
A new mutation, the first one close to the 5′-end of the neurofibromatosis type 1 (NF1) gene, was found when RNA preparations from various cell types of 15 NF1 patients were analysed by reverse transcription and subsequent multiplex polymerase chain reaction. This mutation removes the 84 by of exon 3 precisely from the cDNA. Genomic Southern blots revealed a larger deletion with breakpoints within the introns flanking exon 3. This mutation suggests that the amino-terminal region of neurofibromin is functionally significant. When using this mutation to distinguish the wild type and mutant alleles, their expression could be analysed in neurofibroma fibroblasts, melanocytes from the unaffected skin, and those from a café-au-lait macule. In all these cell types, the products of both alleles were detected, confirming similar results obtained with a different NFl gene mutation.
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References
Ballester R, Marchuk DA, Boguski M, Saulino AM, Letcher R, Wigler M, Collins FS (1990) The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell 63:851–859
Cawthon R, Weiss R, Xu G, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O'Connell P, White R (1990) A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 62:193–201
Chomozynsky P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Korf BR (1994) Fax Transmission of the NNFF International NF1 Genetic Analysis Consortium, March 1994
Marchuk DA, Saulino AM, Tavakkol R, Swaroop M, Wallace MR, Andersen LB, Mitchell AL, Gutmann DH, Boguski M, Collins FS (1991) cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product. Genomics 11:931–940
Martin GA, Viskochil D, Bollag G, McCabe PC, Crosier WJ, Haubruck H, Conroy L, Clark R, O'Connell P, Cawthon RM, Innis MA, McCormick F (1990) The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell 63:843–849
Riccardi VM (1992) Neurofibromatosis: phenotype, natural history, and pathogenesis. Johns Hopkins University Press, Baltimore
Stark M, Assum G, Kaufmann D, Kehrer H, Krone W (1992) Analysis of segregation and expression of an identified mutation at the neurofibromatosis type 1 locus. Hum Genet 90:356–359
Viskochil D, Buchberg AM, Xu G, Stevens J, Wolff RK, Culver M, Carey J, Copeland NG, Jenkins NA, White R, O'Connell P (1990) Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 62:187–192
Wallace MR, Marchuk DA, Andersen LB, Letcher R, Oden HM, Saulino AM, Fountain GW, Brereton A, Nicholson J, Mitchell AL, Brownstein B, Collins FS (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249:181–186
Xu G, Lin B, Tanaka K, Dunn D, Wood D, Gesteland R, White R, Weiss R, Tamanoi F (1990b) The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants ofS. cerevisiae. Cell 63:835–841
Xu G, O'Connell P, Viskochil D, Cawthon R, Robertson R, Culver M, Dunn D, Stevens J, Gesteland R, White R, Weiss R (1990a) The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62:599–608
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Hoffmeyer, S., Assum, G., Kaufmann, D. et al. A deletion in the 5 ′-region of the neurofibromatosis type 1 (NF1) gene. Hum Genet 94, 97–100 (1994). https://doi.org/10.1007/BF02272852
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DOI: https://doi.org/10.1007/BF02272852